Hydrogel microparticle scaffold with gradients of degradability and methods thereof

Abstract

Disclosed herein is a device and method for regenerating tissue using a modular scaffold having a gradient of enzymatic degradability. The disclosure further relates to scaffolds made of microparticles comprising a cross-linked water-soluble polymer or cross-linked water-soluble polymers and a process for forming thereof.

What is claimed is: 
     
       1. A modular scaffold comprising a plurality of hydrogel microparticles, wherein the hydrogel microparticles are crosslinked together with at least some crosslinks having tunable rates of enzymatic degradation, wherein the crosslinks is the plasmin sensitive peptide sequence Ac-GCGGVRNGGK-NH2. 
     
     
       2. The modular scaffold of  claim 1 , wherein the scaffold comprises a gradient of degradation between the microparticles. 
     
     
       3. The modular scaffold of  claim 2 , wherein microparticles with at least two different rates of degradability are layered to form the gradient of degradation in the scaffold. 
     
     
       4. The modular scaffold of  claim 3 , wherein the gradient of degradation has a length scale greater than the mean size of the microparticles. 
     
     
       5. The modular scaffold of  claim 1 , wherein the crosslinks between the microparticles fully degrade before the bulk of the microparticles fully degrades. 
     
     
       6. The modular scaffold of  claim 1 , wherein the microparticles comprise a cross-linked water-soluble polymer. 
     
     
       7. The modular scaffold of  claim 6 , wherein the water-soluble polymer is selected from the group consisting of polyacrylate, polyacrylamide, poly(acrylamide sulphonic acid), polyacrylonitrile, polyamines, poly(ethylene glycol), poly(ethylene imine), poly(ethylene oxide), poly(ethyloxazoline), polyhydroxyethylacrylate, polymethacrylate, polymethacrylamide, poly(oxyalkylene oxide), poly(propylene oxide), polyurethane, poly(vinyl alcohol), poly(vinyl pyrrolidone), and combinations thereof. 
     
     
       8. The modular scaffold of  claim 1 , wherein at least a portion of the crosslinks between the microparticles are formed using Click chemistry. 
     
     
       9. The modular scaffold of  claim 1 , wherein the microparticles further comprise a functional agent. 
     
     
       10. The modular scaffold of  claim 9 , wherein the functional agent is selected from the group consisting of cell adhesion proteins, growth factors, extra cellular matrix components, and combinations thereof. 
     
     
       11. The modular scaffold of  claim 10 , wherein the cell adhesion protein is laminin. 
     
     
       12. The modular scaffold of  claim 11 , wherein the growth factor is glial cell-derived neurotrophic factor (GDNF). 
     
     
       13. The modular scaffold of  claim 12 , wherein the microparticles further comprise heparin. 
     
     
       14. The modular scaffold of  claim 13 , wherein the heparin content of the microparticles is greater than about 3% by weight. 
     
     
       15. The modular scaffold of  claim 9 , wherein the scaffold comprises a concentration gradient of the functional agent. 
     
     
       16. The modular scaffold of  claim 1 , wherein the scaffold is contained within a nerve guidance conduit. 
     
     
       17. The modular scaffold of  claim 1 , wherein the scaffold is seeded with or encourages the in-growth of cells selected from the group consisting of fibroblasts, epithelial cells, blood cells, precursor blood cells, immune system cells, hepatocytes, renal cells, chondrocytes, osteoblasts, respiratory tract cells, gut cells, bladder cells, pancreatic cells, myoblasts, skeletal muscle cells, heart muscle cells, smooth muscle cells, exocrine gland cells, hormone secreting cells, sensory transducer cells, neurons, neuron supporting cells, stem cells, and combinations thereof. 
     
     
       18. The modular scaffold of  claim 17 , wherein the cells are neurons, neuron supporting cells, or combinations thereof.